Our objective is to establish the biochemical basis for radiation-induced mitotic delay. Results obtained to date suggest that exposure of plasmodia of Physarum polycephalum to gamma radiation at 1.25-2h prior to the expected occurrence of metaphase results in a dose-dependent mitotic delay and a corresponding delay in the appearance of peaks of cyclic AMP, histone phosphorylation, and a histone kinase activity. The latter activity can be inhibited by cyclic AMP in vitro. Morphologically, nuclei appear to cease progression toward metaphase at about the time of the radiation marker (the time at which nuclei became refractory to radiation-induced mitotic delay). We plan to further study the interrelationships between these events by irradiation of plasmodia at specific times during late G2 and early prophase and determination of the effects of such exposure on the above parameters. Using this approach we hope ultimately to elucidate the mechanism by which ionizing radiation delays nuclear division.